Endoplasmic reticulum (ER) stress is an important event in atherosclerosis. Recent studies have shown that ER stress deregulates cholesterol metabolism via multiple pathways. This study aimed to determine the relationship between ER stress and lipid metabolism and to verify that upregulation of miR-33 is involved in this process.An atherosclerosis model was established in apolipoprotein E-deficient (ApoE-/-) mice fed a Western diet, and THP-1 derived macrophages were used in this study. Hematoxylin-eosin and Oil Red O staining were used to quantify the atherosclerotic plaques. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate labeled oxidized low-density lipoprotein binding assay and a Cholesterol Efflux Fluorometric Assay Kit were used to observe cholesterol uptake and efflux. The mRNA and protein levels of biomarkers associated with ER stress and cholesterol metabolism in atherosclerotic plaques and macrophages were evaluated by real-time PCR and western blotting, respectively. Immunofluorescence was used to observe alterations of ABCA1 localization. Small interfering RNAs were used to knock down CHOP and miR-33 in macrophages to alter CHOP and miR-33 expression.Atherosclerotic lesions and systemic lipid levels were ameliorated after inhibition of ER stress (tauroursodeoxycholic acid) in vivo. In vitro studies confirmed that ER stress regulated the lipid catabolism of macrophages by promoting cholesterol uptake, inhibiting cholesterol efflux, and modulating the expression of related transporters. CHOP contributed to lipid metabolism disorder following ER stress. Furthermore, over-expression of miR-33 was involved in ER stress that induced lipid metabolism disorder in macrophages. These findings support a model of ER stress induction by oxidized low-density lipoprotein that affects macrophage lipid catabolism disorder.Our data shed new light on the relationship between ER stress and lipid metabolism in vivo and in vitro, and confirm that upregulation of miR-33 is involved in this process. The relationship between ER stress and miR-33 represents a novel target for the treatment of atherosclerosis.
This study aimed to compare the clinical effects of continuous renal replacement therapy (CRRT) and routine therapy in heatshock (HS) patients.We retrospectively reviewed the clinical information of 33 severe exertional HS patients who were treated from February 1998 to October 2013. On the basis of whether or not CRRT therapy was used in addition to conventional therapy, patients were divided into a CRRT group (n = 15) and a control group (n = 18). Body temperature, blood gas analysis, routine blood tests, blood eletrolytes, enzymes and kidney function data, and APACHE II scores were obtained and compared between the 2 groups on admission and 3, 5, and 7 days after admission. Mortality was also compared between the 2 groups.CRRT treatment combined with conventional treatment resulted in a higher hospital-discharge rate, a faster return to normal of body temperature, greater increase in platelets, a greater decrease in WBC, neutrophils, and serum markers for liver and kidney dysfunction, greater improvement of organ dysfunction, and lower APACHE II scores than conventional treatment used alone.The addition of CRRT to conventional treatment for HS improves survival and causes a faster return to normal of serum markers and organ function.
To investigate the relationship of seminal plasma elastase (SPE) with sperm reactive oxygen species (ROS) and semen parameters in infertile men.Between July 2021 and December 2021, a total of 145 subjects aged 20-51 years with male infertility were enrolled. SPE, seminal leukocytes, sperm ROS, DNA fragmentation index (DFI) and other semen parameters were detected. We divided patients into an inflammation group (SPE ≥ 290 ng/ml, n = 48) and a non-inflammation group (SPE < 290 ng/ml, n = 97), analyzed the relationship of SPE with seminal leukocytes, sperm ROS, semen volume, sperm concentration, total sperm motility, the percentages of progressively motile sperm (PMS) , morphologically normal sperm (MNS), and DFI.The concentration of seminal leukocytes, sperm ROS level and DFI were significantly higher in inflammation group than in non-inflammation group (P < 0.05). No statistically significant differences were observed in semen volume, sperm concentration, total sperm motility, PMS, MNS or sperm deformity index (SDI) between two groups of patients (P > 0.05). Spearman correlation analysis showed that the SPE level was correlated positively with the concentration of seminal leukocytes (r = 0.658, P < 0.01), sperm ROS level (r = 0.229, P = 0.006) and DFI (r = 0.192, P = 0.021), but not correlated with semen volume, sperm concentration, total sperm motility, PMS, MNS or SDI (P > 0.05).The level of seminal plasma elastase is related with the concentration of seminal leukocytes, sperm ROS level and DFI, and has some reference value in the diagnosis of male infertility.
Background and objective: Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular procedures and is associated with substantial morbidity and mortality. While the preventative measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches. The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CIAKI. We previously demonstrated that valsartan alleviated CM-induced human renal tubular cell apoptosis by inhibiting ER stress in vitro. However, the nephroprotective effect of valsartan on CI-AKI in vivo has not been investigated. Therefore, the aim of this study was to explore the protective effect of valsartan in a rat model of CI-AKI by measuring the amelioration of renal damage and the changes in ER stressrelated biomarkers. Method and Results: Our results showed that the radiocontrast agent meglumine diatrizoate caused significant renal insufficiency, renin-angiotensin system (RAS) activation, and renal tubular apoptosis by triggering ER stress through activation of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), caspase 12, CCAAT/enhancer-binding protein-homologous protein (CHOP) and c-Jun N-terminal protein kinase (JNK) (P<0.05; n=6 in each group). Pre-treatment with valsartan significantly alleviated renal dysfunction, pathological injury, and apoptosis along with the inhibition of ER stressrelated biomarkers (P<0.05; n=8 in each group). Conclusion: Valsartan could protect against meglumine diatrizoate-induced kidney injury in rats by inhibiting the ER stress-induced apoptosis, making it a promising strategy for preventing CI-AKI. Keywords: Contrast-induced acute kidney injury, endoplasmic reticulum stress, apoptosis, valsartan.
Dengue imposes a heavy economic burden on families and society. We used surveillance data reported in 2019 to characterize the dengue epidemic in Zhejiang Province, China, which provided guidance for dengue prevention and control. Dengue epidemics mostly occurred in July to October. People aged 30-44 years, males, and commercial service workers were more likely to suffer from dengue. The epidemic areas were mainly in Hangzhou and Wenzhou. Meanwhile, we assessed the economic cost of dengue in the province from both family and organizational perspectives. The direct economic burden of dengue patients was estimated to be USD 405,038.25, and the indirect economic burden was USD 140,364.90, for a total economic burden of USD 543,213.00. The direct economic burden of dengue patients should be reduced by increasing the coverage and reimbursement of health insurance. Additionally, the total annual cost of dengue prevention and control for the government and organizational sectors was estimated to be USD 7075,654.83. Quantifying the dengue burden is critical for developing disease control strategies, allocating public health resources, and setting health policy priorities.
Abstract Aims To perform an updated systematic review and meta‐analysis of postoperative delirium (POD) after transcatheter aortic valve replacement (TAVR). Methods We conducted a systematic literature search of PubMed, Embase, and Cochrane Library databases from the time of the first human TAVR procedure in 2002 until December 24, 2021, which was supplemented by manual searches of bibliographies. Data were collected on incidence rates, risk factors, and/or associated mortality of POD after TAVR. Pooled analyses were conducted using random effects models to yield mean differences, odds ratios, hazard ratios, and risk ratios, with 95% confidence intervals. Results A total of 70 articles (69 studies) comprising 413,389 patients were included. The study heterogeneity was substantial. The pooled mean incidence of POD after TAVR in all included studies was 9.8% (95% CI: 8.7%–11.0%), whereas that in studies using validated tools to assess for delirium at least once a day for at least 2 consecutive days after TAVR was 20.7% (95% CI: 17.8%–23.7%). According to the level of evidence and results of meta‐analysis, independent preoperative risk factors with a high level of evidence included increased age, male sex, prior stroke or transient ischemic attack, atrial fibrillation/flutter, weight loss, electrolyte abnormality, and impaired Instrumental Activities of Daily Living; intraoperative risk factors included non‐transfemoral access and general anesthesia; and acute kidney injury was a postoperative risk factor. POD after TAVR was associated with significantly increased mortality (pooled unadjusted RR: 2.20, 95% CI: 1.79–2.71; pooled adjusted RR: 1.62, 95% CI: 1.25–2.10), particularly long‐term mortality (pooled unadjusted HR: 2.84, 95% CI: 1.91–4.23; pooled adjusted HR: 1.88, 95% CI: 1.30–2.73). Conclusions POD after TAVR is common and is associated with an increased risk of mortality. Accurate identification of risk factors for POD after TAVR and implementation of preventive measures are critical to improve prognosis.
Abstract Background Allergic rhinitis is a common health concern that affects quality of life. This study aims to examine the online search trends of allergic rhinitis in China before and after the COVID-19 epidemic and to explore the association between the daily air quality and online search volumes of allergic rhinitis in Beijing. Methods We extracted the online search data of allergic rhinitis-related keywords from the Baidu index database from January 23, 2017 to June 23, 2022. We analyzed and compared the temporal distribution of online search behaviors across different themes of allergic rhinitis before and after the COVID-19 pandemic in mainland China, using the Baidu search index (BSI). We also obtained the air quality index (AQI) data in Beijing and assessed its correlation with daily BSIs of allergic rhinitis. Results The online search for allergic rhinitis in China showed significant seasonal variations, with two peaks each year in spring from March to May and autumn from August and October. The BSI of total allergic rhinitis-related searches increased gradually from 2017 to 2019, reaching a peak in April 2019, and declined after the COVID-19 pandemic, especially in the first half of 2020. The BSI for all allergic rhinitis themes was significantly lower after the COVID-19 pandemic than before (all p values < 0.05). The results also revealed that, in Beijing, there was a significant negative association between daily BSI and AQI for each allergic rhinitis theme during the original variant strain epidemic period and a significant positive correlation during the Omicron variant period. Conclusion Both air quality and the interventions used for COVID-19 pandemic, including national and local quarantines and mask wearing behaviors, may have affected the incidence and public concern about allergic rhinitis in China. The online search trends of allergic rhinitis can provide useful information for health authorities and professionals to monitor the public needs and interests and to deliver timely and tailored health education and prevention strategies.
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